dbSNP rs7505: EVI2A:c.*469C>T (chr17-31317834-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014210.4(EVI2A):c.*469C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 152,988 control chromosomes in the GnomAD database, including 20,966 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.50 ( 20794 hom., cov: 32)

Exomes 𝑓: 0.54 ( 172 hom. )

Consequence

EVI2A
NM_014210.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.43

Publications

15 publications found

Variant links:

Genes affected

EVI2A (HGNC:3499): (ecotropic viral integration site 2A) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

EVI2A links:

NF1 (HGNC:7765): (neurofibromin 1) This gene product appears to function as a negative regulator of the ras signal transduction pathway. Mutations in this gene have been linked to neurofibromatosis type 1, juvenile myelomonocytic leukemia and Watson syndrome. The mRNA for this gene is subject to RNA editing (CGA>UGA->Arg1306Term) resulting in premature translation termination. Alternatively spliced transcript variants encoding different isoforms have also been described for this gene. [provided by RefSeq, Jul 2008]

NF1 Gene-Disease associations (from GenCC):

neurofibromatosis type 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia, G2P, Genomics England PanelApp
neurofibromatosis-Noonan syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, PanelApp Australia
Moyamoya disease
Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
hereditary pheochromocytoma-paraganglioma
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
familial ovarian cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

NF1 links:

ENSG00000265118 (HGNC:):

ENSG00000265118 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
EVI2A	NM_014210.4 link	c.*469C>T	3_prime_UTR_variant	Exon 2 of 2	ENST00000462804.3	NP_055025.2	P22794-1
NF1	NM_001042492.3 link	c.4836-7986G>A	intron_variant	Intron 36 of 57	ENST00000358273.9	NP_001035957.1	P21359-1
EVI2A	NM_001003927.3 link	c.*469C>T	3_prime_UTR_variant	Exon 3 of 3		NP_001003927.1	P22794-2
NF1	NM_000267.4 link	c.4773-7986G>A	intron_variant	Intron 35 of 56		NP_000258.1	P21359-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
EVI2A	ENST00000462804.3 link	c.*469C>T	3_prime_UTR_variant	Exon 2 of 2	1	NM_014210.4	ENSP00000420557.3	P22794-1
NF1	ENST00000358273.9 link	c.4836-7986G>A	intron_variant	Intron 36 of 57	1	NM_001042492.3	ENSP00000351015.4	P21359-1
ENSG00000265118	ENST00000578584.5 link	c.478+474C>T	intron_variant	Intron 1 of 2	2		ENSP00000463981.2	J3QR06

Frequencies

GnomAD3 genomes

AF:

0.501

AC:

76012

AN:

151788

Hom.:

20786

Cov.:

show subpopulations

Gnomad AFR

AF:

0.287

Gnomad AMI

AF:

0.678

Gnomad AMR

AF:

0.445

Gnomad ASJ

AF:

0.684

Gnomad EAS

AF:

0.360

Gnomad SAS

AF:

0.570

Gnomad FIN

AF:

0.602

Gnomad MID

AF:

0.605

Gnomad NFE

AF:

0.620

Gnomad OTH

AF:

0.532

GnomAD4 exome

AF:

0.538

AC:

582

AN:

1082

Hom.:

172

Cov.:

AF XY:

0.534

AC XY:

314

AN XY:

588

show subpopulations

African (AFR)

AF:

0.167

AC:

AN:

American (AMR)

AF:

0.371

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.688

AC:

AN:

East Asian (EAS)

AF:

0.250

AC:

AN:

South Asian (SAS)

AF:

0.524

AC:

AN:

168

European-Finnish (FIN)

AF:

0.556

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.569

AC:

427

AN:

750

Other (OTH)

AF:

0.421

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.501

AC:

76045

AN:

151906

Hom.:

20794

Cov.:

AF XY:

0.498

AC XY:

36981

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.287

AC:

11905

AN:

41442

American (AMR)

AF:

0.445

AC:

6783

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.684

AC:

2373

AN:

3470

East Asian (EAS)

AF:

0.360

AC:

1858

AN:

5164

South Asian (SAS)

AF:

0.568

AC:

2736

AN:

4818

European-Finnish (FIN)

AF:

0.602

AC:

6337

AN:

10528

Middle Eastern (MID)

AF:

0.603

AC:

176

AN:

292

European-Non Finnish (NFE)

AF:

0.620

AC:

42144

AN:

67924

Other (OTH)

AF:

0.529

AC:

1116

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1800

3601

5401

7202

9002

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

672

1344

2016

2688

3360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.586

Hom.:

31572

Bravo

AF:

0.478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

(source)

DANN

Benign

0.39

PhyloP100

2.4

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over